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Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and overNCINCI-2012-01149
CDR0000730114, UCCRC-IL057, 12-0109, 9012, U01CA070095, N01CM00071, N01CM00038, U01CA062491, N01CM00039, P30CA014599, IL057, NCT01576172

Trial Description

Summary

This randomized phase II trial studies abiraterone acetate and prednisone together with veliparib to see how well it works compared to abiraterone acetate and prednisone alone in treating patients with metastatic hormone-resistant prostate cancer. Androgens can cause the growth of prostate cancer cells. Antiandrogen drugs, such as abiraterone acetate, may lessen the amount of androgens made by the body. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving abiraterone acetate together with prednisone and veliparib is more effective than abiraterone acetate and prednisone alone in treating prostate cancer.

Further Study Information

PRIMARY OBJECTIVES:

I. To evaluate the role of v-ets erythroblastosis virus E26 oncogene (ETS) gene fusion as a predictive biomarker for response to hormone therapy (abiraterone [abiraterone acetate]) alone or hormone therapy plus poly adenosine diphosphate-ribose polymerase 1 (PARP-1) targeted therapy (ABT-888 [veliparib]) in patients with metastatic castration resistant prostate cancer.

II. To evaluate whether the addition of PARP-1 targeted therapy is superior to hormone therapy alone based on ETS gene fusion status.

SECONDARY OBJECTIVES:

I. Rate of prostate-specific antigen (PSA) declines. II. Objective response rate. III. Progression-free survival. IV. Evaluate the qualitative and quantitative toxicity of abiraterone acetate with and without ABT-888.

TERTIARY OBJECTIVES:

I. To determine the concordance in fusion status among prostate cancer samples from the primary site, biopsied metastasis, and circulating tumor cells (CTCs).

II. To assess if ETS fusion status in the CTCs, at baseline, 12 weeks, and disease progression (or when off study) is associated with response to therapy.

III. To evaluate if the number of CTCs, as well as the expression levels of androgen receptor, RAD51 recombinase (RAD51), and gamma-H2A histone family, member X (H2aX) foci in the CTCs at baseline, at 12 weeks, and at disease progression in all patients is associated with response to therapy.

IV. To determine the role of phosphatase and tensin homolog (PTEN) loss as a predictive biomarker of response to abiraterone, alone or in combination with ABT-888.

V. To determine the role of PARP1 activity as a predictive biomarker of response to abiraterone, alone or in combination with ABT-888.

VI. To perform next-generation sequencing for discovery of novel gene fusions in prostate cancers negative for ETS fusions.

VII. To perform germline single nucleotide polymorphism (SNP) analysis of genes involved in hormone synthesis, transport, binding, metabolism, and degradation for discovery of novel SNPs predictive of response to abiraterone, alone or in combination with ABT-888.

VIII. To determine if ETS fusion ribonucleic acid (RNA) levels in blood are predictive of response to abiraterone, alone or in combination with ABT-888.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive abiraterone acetate orally (PO) once daily (QD) and prednisone PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1).Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 2 years.

Eligibility Criteria

Inclusion Criteria:

  • Have a histologic or cytologic diagnosis of prostate cancer
  • Have progressive metastatic castration-resistant prostate cancer, on androgen-deprivation therapy, based on at least one of the following criteria:
  • PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1-week interval with a minimum PSA of 2 ng/mL
  • Progression of bidimensionally measurable soft tissue (nodal metastasis) assessed within one month prior to registration by a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen and pelvis
  • Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scan
  • Agree to undergo a biopsy of at least 1 metastatic site for gene-fusion status analysis; adequate archival metastatic tissue can be used if available in lieu of a biopsy; patients will only be eligible for protocol therapy if the biopsy has tumor and the tissue is evaluable for ETS fusion status
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Have testosterone < 50 ng/dL; patients must continue primary androgen-deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy
  • Patients must discontinue antiandrogen therapy for at least 4 weeks (e.g. flutamide, bicalutamide, nilutamide) prior to registration with no evidence of a falling PSA after washout; patients on steroids are eligible as long as they will be switched to prednisone
  • Have no prior exposure to cytochrome 450 family 17(CYP-17) (other than ketoconazole) or PARP inhibitors for prostate cancer; patients with prior exposure to ketoconazole are eligible
  • Patients with up to 2 prior chemotherapy regimens are eligible
  • White blood cells (WBC) >= 3,000/uL
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Platelet count >= 100,000/uL
  • Serum creatinine =< 1.5 x the institutional upper limits of normal or corrected creatinine clearance of >= 50 mg/ml/hr/1.73 m^2 body surface area (BSA)
  • Potassium >= 3.5 mmol/L
  • Bilirubin within the institutional limits of normal
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 times upper limit of normal
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 times upper limit of normal
  • Must agree to use effective contraception during treatment and for at least 1 week after the last administration of therapy
  • Patients must be able to take oral medication without crushing, dissolving, or chewing tablets
  • Patients may have received prior radiation therapy or surgery; however, at least 21 days must have elapsed since completion of radiation therapy or surgery and patient must have recovered from all side effects at the time of registration
  • Ability to understand and the willingness to sign a written informed-consent document that is approved by the local institutional review board

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents; any prior investigational products must be stopped at least 14 days (2-week washout) prior to registration
  • Patients who have had chemotherapy, radiotherapy or oral antifungal agents (Ketoconazole, itraconazole, fluconazole) within 3 weeks prior to entering the study or those who have not recovered (e.g. back to baseline or grade 1) from adverse events due to agents administered more than 3 weeks earlier
  • There is a potential drug interaction when abiraterone is concomitantly used with a cytochrome P450 family 2, subfamily D, polypeptide 6 (CYP2D6) substrate narrow therapeutic index (e.g., thioridazine, dextromethorphan), or strong cytochrome P450 family 3, subfamily A, polypeptide 4 [CYP3A4] inhibitors (e.g., atazanavir, erythromycin, indinavir, itraconazole, Ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) or strong inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine); caution should be used when patients are on one of these drugs
  • Patients with history of active seizures are not eligible
  • Patients with a history of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis, or chronic liver disease are not eligible
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or abiraterone
  • Patients may continue on a daily multi-vitamin, calcium and vitamin D, but all other herbal, alternative and food supplements (i.e. PC-Spes, Saw Palmetto, St John's wort, etc.) must be discontinued before registration; patients must not be planning to receive any concurrent cytotoxic chemotherapy, surgery, or radiation therapy during protocol treatment; hormonal-acting agents (including diethylstilbestrol/DES, aldosterone, and spironolactone) are forbidden during the trial and must be stopped prior to registration; no washout period will be required for any of these agents; patients on megestrol acetate for hot flashes are allowed to continue therapy
  • Patients on stable doses of bisphosphonates or denosumab which have been started prior to registration may continue on this medication, patients who are not on bisphosphonates or denosumab are eligible as long as they initiate therapy prior to registration
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or concurrent medications that alter cardiac conduction
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible; patients are not considered to have a "currently active" malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Maha HussainPrincipal Investigator

Trial Sites

U.S.A.
California
  Duarte
 City of Hope Comprehensive Cancer Center
 Przemyslaw W. Twardowski Ph: 626-256-4673
  Email: ptwardowski@coh.org
 Przemyslaw W. TwardowskiPrincipal Investigator
  Los Angeles
 USC/Norris Comprehensive Cancer Center and Hospital
 David I. Quinn Ph: 323-865-3956
  Email: diquinn@usc.edu
 David I. QuinnPrincipal Investigator
  Pasadena
 City of Hope Medical Group
 Stephen C. Koehler Ph: 626-396-2900
  Email: skhoehler@cohmg.com
 Stephen C. KoehlerPrincipal Investigator
Illinois
  Chicago
 University of Chicago Cancer Research Center
 Walter M. Stadler Ph: 773-702-4150
  Email: wstadler@medicine.bsd.uchicago.edu
 Walter M. StadlerPrincipal Investigator
  Evanston
 CCOP - Evanston
 Daniel H. Shevrin Ph: 847-570-2515
  Email: DShevrin@northshore.org
 Daniel H. ShevrinPrincipal Investigator
Indiana
  Indianapolis
 Indiana University Melvin and Bren Simon Cancer Center
 Costantine Albany Ph: 317-948-8310
  Email: calbany@iupui.edu
 Costantine AlbanyPrincipal Investigator
Maryland
  Baltimore
 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
 Emmanuel S. Antonarakis Ph: 410-502-7528
  Email: eantona1@jhmi.edu
 Emmanuel S. AntonarakisPrincipal Investigator
Michigan
  Ann Arbor
 University of Michigan Comprehensive Cancer Center
 Maha H. Hussain Ph: 734-936-8906
  Email: mahahuss@umich.edu
 Maha Hadi A. HussainPrincipal Investigator
New Jersey
  New Brunswick
 Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
 Mark N. Stein Ph: 732-235-3336
  Email: steinmn@umdnj.edu
 Mark SteinPrincipal Investigator
North Carolina
  Chapel Hill
 Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
 Young E. Whang Ph: 919-843-9983
  Email: ywhang@med.unc.edu
 Young E. WhangPrincipal Investigator
Texas
  Houston
 M. D. Anderson Cancer Center at University of Texas
 Paul G. Corn Ph: 713-792-2830
  Email: pcorn@mdanderson.org
 Paul G. CornPrincipal Investigator
Washington
  Seattle
 University Cancer Center at University of Washington Medical Center
 Robert B. Montgomery Ph: 206-598-0860
  Email: rbmontgo@u.washington.edu
 Robert B. MontgomeryPrincipal Investigator
Wisconsin
  Wisconsin Rapids
 Riverview UW Cancer Center at Riverview Hospital
 Glenn Liu Ph: 608-265-8689
  Email: gxl@medicine.wisc.edu
 Glenn LiuPrincipal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01576172
ClinicalTrials.gov processed this data on March 17, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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